Our current understanding of pain mechanisms is based principally on experimental investigations of cutaneous pain. Less well understood are mechanisms of deep pain arising from joints, muscle and particularly the viscera. Visceral pain in general is more important clinically than is cutaneous pain, but we know considerably less about visceral pain mechanisms and its control than we do about cutaneous pain mechanisms. Over the past 10 years or so, there has been increased interest in deep pain mechanisms, and we and other laboratories have contributed to improved understanding of visceral pain mechanisms. Specifically, this project has in the past addressed cardiac, esophageal, gastric and colonic nociception. Colorectal distension (CRD) is the model with which we have worked most and which has been best characterized. Experiments proposed for the next project period will continue to examine mechanisms of visceral nociception and its modulation. Specific Aims include: (1) quantitative characterization of responses of myelinated and unmyelinated least splanchnic and pelvic nerve sensory afferent fibers to graded CRD; (2) modulation of sensory afferent fiber responses to CRD by opioid and somatostatin receptor agonists; (3) evaluation of the central (spinal) mediators of visceral nociceptive transmission; and (4) assessment by intracellular analysis of the cellular properties of spinal units that respond to CRD. These Specific Aims are a logical extension of the current project and will continue important investigations into the mechanisms of visceral pain and its modulation. The proposed experiments comprise a quantitative, parametric examination of visceral sensory afferent and spinal cord physiology and pharmacological modulation of visceral nociception that will lead to better understanding of the mechanisms and control of visceral pain.